BackgroundPeru's HIV epidemic is concentrated among men who have sex with men (MSM). The contribution of alcohol use disorders (AUDs) to known high-risk behaviors associated with HIV transmission in this context has not been well characterized.MethodsBetween June and October 2011, 5,148 sexually active MSM were recruited using convenience sampling in five cities to participate in a cross-sectional bio-behavioral survey. Five high-risk sexual criteria previously associated with incident HIV infection in this setting were selected a priori as the dependent outcomes. Screening for AUDs used the validated Alcohol Use Disorders Identification Test (AUDIT) and AUDS were stratified by severity. Unadjusted and adjusted odds ratios (AOR) were computed to establish the independent correlates of the five dependent outcomes.ResultsThe majority (62.8%) of participants met screening criteria for having an AUD, which were independently correlated with each of the following high-risk sexual risk behaviors in the previous 6 months: 1) >5 sexual partners [AOR = 1.76; (1.54–2.02)]; 2) sex with an HIV-infected partner [AOR = 1.29; (1.03–1.62)]; 3) having a sexually transmitted infection [AOR = 1.38; (1.13–1.68)]; 4) being a sex worker [AOR = 1.61; (1.40–1.87)]; and 5) unprotected sex during last encounter [AOR = 1.22; (1.09–1.38)]. Recent drug use was also correlated with having >5 sexual partners [AOR = 1.42 (1.19–1.71)], sex work [AOR = 1.97 (1.63–2.39)] and unprotected sex during last encounter [AOR = 1.31 (1.11–1.54)]. For each dependent variable, the association with AUDs significantly increased with increasing AUD severity.ConclusionsAUDs are highly prevalent among MSM in Peru and are associated with increased HIV risk-taking behaviors that are associated with HIV transmission. Strategies that target problematic drinking such as medication-assisted therapy, behavioral counseling and structural interventions could potentially reduce risky behaviors and ultimately reduce HIV transmission among MSM in Peru.

PURPOSE Pembrolizumab significantly improves clinical outcomes in advanced/metastatic microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumors but is not well studied in the neoadjuvant space. METHODS This is a phase II open-label, single-center trial of localized unresectable or high-risk resectable MSI-H/dMMR tumors. Treatment is pembrolizumab 200 mg once every 3 weeks for 6 months followed by surgical resection with an option to continue therapy for 1 year followed by observation. To continue on study, patients are required to have radiographic or clinical benefit. The coprimary end points are safety and pathologic complete response. Key secondary end points are response rate and organ-sparing at one year for patients who declined surgery. Exploratory analyses include interrogation of the tumor immune microenvironment using imaging mass cytometry. RESULTS A total of 35 patients were enrolled, including 27 patients with colorectal cancer and eight patients with noncolorectal cancer. Among 33 evaluable patients, best overall response rate was 82%. Among 17 (49%) patients who underwent surgery, the pathologic complete response rate was 65%. Ten patients elected to receive one year of pembrolizumab followed by surveillance without surgical resection (median follow-up of 23 weeks [range, 0-54 weeks]). An additional eight did not undergo surgical resection and received less than 1 year of pembrolizumab. During the study course of the trial and subsequent follow-up, progression events were seen in six patients (four of whom underwent salvage surgery). There were no new safety signals. Spatial immune profiling with imaging mass cytometry noted a significantly closer proximity between granulocytic cells and cytotoxic T cells in patients with progressive events compared with those without progression. CONCLUSION Neoadjuvant pembrolizumab in dMMR/MSI-H cancers is safe and resulted in high rates of pathologic, radiographic, and endoscopic response, which has implications for organ-sparing strategies.

Immune checkpoint inhibition (CPI) for metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) demonstrates high clinical activity that appears durable, but the impact of CPI on pathological tumor response is unknown. In this retrospective analysis, our objective was to assess pathological response and clinical outcomes in dMMR mCRC patients treated with CPI prior to surgical resection of primary and/or metastatic tumor. Among 121 advanced dMMR mCRC patients treated with CPI at 2 institutions between November 2016 and December 2018, 14 underwent surgery. Pathologic complete response was noted in the resected specimens of 13 patients despite the presence of residual tumor on preoperative imaging in 12 of those patients. With median follow-up of 9 months, no patients have had disease relapse or progression. For this small retrospective study, the data suggest that residual radiographic tumor may not require systematic resection following response to anti-PD1–based therapy. However, larger prospective studies are warranted.

This study compared the correlates of HIV risk among men who have sex with men (MSM) with newly diagnosed versus previously known HIV infection among 5,148 MSM recruited using modified snowball sampling in 5 Peruvian cities. Participants, if age≥18 years and sex with a male in the previous 12 months, underwent standardized computer-assisted risk assessments and HIV and syphilis testing. Overall, 420 (8.2%) participants tested HIV seropositive, most of whom (89.8%) were unaware of their HIV status. Compared to those who knew themselves to be HIV-infected, multivariate logistic regression demonstrated that unprotected anal intercourse at last encounter [AOR=2.84 (95% CI 1.09–7.40)] and having an alcohol use disorder (AUD) [AOR=2.14 (95% CI 1.01–5.54)] were independently associated with a newly diagnosed HIV infection. Being unaware of being HIV-infected was associated with high-risk sexual behaviors and AUDs, both of which are amenable to behavioral and medication-assisted therapy interventions.

BackgroundManagement of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.MethodsWe performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.ResultsWe identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04).ConclusionTargeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299,NCT03999749).